Mutations in the human α-tectorin gene cause autosomal dominant non-syndromic hearing impairment

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  • A Correction to this article was published on 01 April 1999

Abstract

The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals, α-tectorin is one of the major non-collagenous components of the tectorial membrane1,2. Recently, the gene encoding mouse α-tectorin (Tecta) was mapped to a region of mouse chromosome 9, which shows evolutionary conservation with human chromosome 11q (ref. 3), where linkage was found in two families, one Belgian (DFNA12; ref. 4) and the other, Austrian (DFNA8; unpublished data), with autosomal dominant non-syndromic hearing impairment. We determined the complete sequence and the intron-exon structure of the human TECTA gene. In both families, mutation analysis revealed mis-sense mutations which replace conserved amino-acid residues within the zona pellucida domain of TECTA. These findings indicate that mutations in TECTA are responsible for hearing impairment in these families, and implicate a new type of protein in the pathogenesis of hearing impairment.

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References

  1. 1

    Richardson, G.P., Russell, I.J., Duance, V.C. & Bailey, A.J. Polypeptide composition of the mammalian tectorial membrane. Hear. Res. 25, 45–60 (1987).

  2. 2

    Legan, P.K., Rau, A., Keen, J.N. & Richardson, G.P. The mouse tectorins. Modular matrix proteins of the inner ear homologous to components of the sperm-egg adhesion system. J. Biol. Chem. 272, 8791–8801 (1997).

  3. 3

    Hughes, D.C., Legan, P.K., Steel, K.P. & Richardson, G.P. Mapping of the alpha tectorin gene to mouse chromosome 9 and human chromosome 11 : A candidate for human autosomal dominant non-syndromic deafness. Genomics 48, 46–51 (1998).

  4. 4

    Verhoeven, K. et al. A gene for autosomal dominant non-syndromic hearing loss (DFNA12) maps to chromosome 11q22-24. Am. J. Hum. Genet. 60, 1168–1174 (1997).

  5. 5

    Krawczak, M.(., Reiss, J. & Cooper, D.N. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum. Genet. 90, 41–54 (1992).

  6. 6

    Durkin, M.E. et al. Amino-acid sequence and domain structure of entactin. Homology with epidermal growth factor precursor and low density lipoprotein receptor. J. Cell Biol. 107, 2749–2756 (1988).

  7. 7

    Hardy, D.M. & Garbers, D.L. A sperm membrane protein that binds in a species-specific manner to the egg extracellular matrix is homologous to von Willebrand factor. J. Biol. Chem. 270, 26025–26028 (1995).

  8. 8

    Bork, P. & Sander, C. A large domain common to sperm receptors (Zp2 and Zp3) and TGF-beta type III receptor. FEBS Lett. 300, 237–240 (1992).

  9. 9

    Hession, C. et al. Uromodulin (Tamm-Horsfall glycoprotein) : a renal ligand for lymphokines. Science 237, 1479–1484 (1987}.

  10. 10

    Prasasan, K. et al. Nucleotide sequence and peptide motifs of mouse uromodulin (Tamm-Horsfall protein)-the most abundant protein in mammalian urine. Biochim. Biophys. Acta 1260, 328–332 (1995).

  11. 11

    Fukuoka, S., Freedman, S.D. & Scheele, G.A. A single gene encodes membrane-bound and free forms of GP-2, the major glycoprotein in pancreatic secretory (zymogen) granule membranes. Proc. Natl. Acad. Sci. USA 88, 2898–2902 (1991).

  12. 12

    Yu, H., Papa, F. & Sukhatme, V.P. Bovine and rodent Tamm-Horsfall protein (THP) genes: cloning, structural analysis, and promoter identification. Gene Expr. 4, 63–75 (1994).

  13. 13

    Fukuoka, S., Freedman, S.D., Heron, Y., Sukhatme, V.P. & Scheele, G.A. Gp-2/THP gene family encodes self-binding glycosylphosphatidylinositol-anchored proteins in apical secretory compartments of pancreas and kidney. Proc Natl. Acad. Sci. USA 89, 1189–1193 (1992).

  14. 14

    Wong, S.M. & Lowe, A.W. Sequence of the cDNA encoding human GP-2, the major membrane protein in the secretory granule of the exocrine pancreas. Gene 171, 311–312 (1996).

  15. 15

    Hoops, T.C. & Rindler, M.J. Isolation of the cDNA encoding glycoprotein-2 (GP-2), the major zymogen granule membrane protein, homology to uromodulin/Tamm-Horsfall protein. J. Biol. Chem. 266, 4257–4263 (1991).

  16. 16

    Brown, D.D. et al. The thyroid hormone-induced tail resorption program during Xenopus laevis metamorphosis. Proc. Natl. Acad. Sci. USA 93, 1924–1929 (1996).

  17. 17

    Sulik, K.K. . in Hereditary Hearing Loss and its Syndromes Ch. 4, (eds Gorlin R.J., Toriello, H.V. & Cohen, M.M.) 22–23 (Oxford Univ. Press, Oxford, 1995).

  18. 18

    Govaerts, P.J. et al. A new autosomal dominant locus (DFNA12) is responsible for a non-syndromic, mid-frequency, prelingual and non-progressive sensorineural hearing loss. Am. J. Otol. (In press).

  19. 19

    Lerach, H. et al, in Genome Analysis 1, (eds Davies, K.E. & Tilghman, S.M.) 39–81 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1990).

  20. 20

    Orita, Y., Sekiya, T. & Hayashi, K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics 5, 874–879 (1989).

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Correspondence to Guy Van Camp.

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